Modified PAMAM dendrimer with 4-carbomethoxypyrrolidone surface groups-its uptake, efflux, and location in a cell

Janaszewska, Anna; Studzian, Maciej; Petersen, Johannes F.; Ficker, Mario; Paolucci, Valentina; Christensen, Jørn B.; Tomalia, Donald A.; Klajnert‐Maculewicz, Barbara

doi:10.1016/j.colsurfb.2017.07.052

Cited by 33 publications

(22 citation statements)

References 13 publications

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“…Furthermore, aggregation of hydrophobic fluorophores followed by self‐quenching and photo bleaching also highly influence their optical performance and hinder utility for in vivo applications. [ 11–13 ]…”

Section: Methodsmentioning

confidence: 99%

“…followed by self-quenching and photo bleaching also highly influence their optical performance and hinder utility for in vivo applications. [11][12][13] To address these limitations, several IF-PAMAMs have been designed, as exemplified by 1-(4-carbomethyoxy) pyrrolidoneterminated dendrimers and chemically oxidized hydroxylterminated PAMAM dendrimers. [12,14,15] However, these probes have only been tested in vitro without further validation in vivo.…”

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confidence: 99%

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A Robust Intrinsically Green Fluorescent Poly(Amidoamine) Dendrimer for Imaging and Traceable Central Nervous System Delivery in Zebrafish

Wang

Zhao

et al. 2020

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Poly(amidoamine) (PAMAM) dendrimers have been widely used for CNS (central nervous system)-targeted drug delivery due to their small size and physical characteristics such as being highly branched, mono-dispersed, and allowing a wide range of functional agents to be attached to their surface. [1-4] Transformation of PAMAM-based nanocarriers to enable traceability by multifunctional imaging technologies will expand applications in tracing and targeted drug delivery. [5,6] Many efforts have been made to achieve visual detection of PAMAM dendrimers, mostly through covalent attachment of fluorophores such as fluorescein isothiocyanate (FITC) and cyanine dyes (e.g., Cy5), onto dendritic scaffolds. [7-9] However, fluorophore-conjugation may affect the size, mobility, surface structure, biocompatibility, and solubility of the PAMAM. [10] In addition, the undesired dissociation of the optical probe from the dendrimer prior to reach the specific targets may also compromise its optical stability. Furthermore, aggregation of hydrophobic fluorophores Intrinsically fluorescent poly(amidoamine) dendrimers (IF-PAMAM) are an emerging class of versatile nanoplatforms for in vitro tracking and bio-imaging. However, limited tissue penetration of their fluorescence and interference due to auto-fluorescence arising from biological tissues limit its application in vivo. Herein, a green IF-PAMAM (FGP) dendrimer is reported and its biocompatibility, circulation, biodistribution and potential role for traceable central nervous system (CNS)-targeted delivery in zebrafish is evaluated, exploring various routes of administration. Key features of FGP include visible light excitation (488 nm), high fluorescence signal intensity, superior photostability and low interference from tissue auto-fluorescence. After intravenous injection, FGP shows excellent imaging and tracking performance in zebrafish. Further conjugating FGP with transferrin (FGP-Tf) significantly increases its penetration through the blood-brain barrier (BBB) and prolongs its circulation in the blood stream. When administering through local intratissue microinjection, including intracranial and intrathecal injection in zebrafish, both FGP and FGP-Tf exhibit excellent tissue diffusion and effective cellular uptake in the brain and spinal cord, respectively. This makes FGP/FGP-Tf attractive for in vivo tracing when transporting to the CNS is desired. The work addresses some of the major shortcomings in IF-PAMAM and provides a promising application of these probes in the development of drug delivery in the CNS.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

A Robust Intrinsically Green Fluorescent Poly(Amidoamine) Dendrimer for Imaging and Traceable Central Nervous System Delivery in Zebrafish

Wang

Zhao

et al. 2020

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“…The study revealed great enhancement in the transport of naproxen conjugates across Caco-2 cell monolayers, for both lauroyl and DEG derivatives, and for PAMAM-G0 and PAMAM-G3, while PAMAM-G0 conjugates also presented low cytotoxicities. Pyrrolidone as a new surface modifier has also been employed [ 39 , 40 ]. Half-generation anionic PAMAM has been proven to possess very low cytotoxicity, lytic, and hemolytic properties in a broad concentration range.…”

Section: Toxicity and Safety Concernsmentioning

confidence: 99%

New Advances in General Biomedical Applications of PAMAM Dendrimers

et al. 2018

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Dendrimers are nanoscopic compounds, which are monodispersed, and they are generally considered as homogeneous. PAMAM (polyamidoamine) was introduced in 1985, by Donald A. Tomalia, as a new class of polymers, named ‘starburst polymers’. This important contribution of Professor Tomalia opened a new research field involving nanotechnological approaches. From then on, many groups have been using PAMAM for diverse applications in many areas, including biomedical applications. The possibility of either linking drugs and bioactive compounds, or entrapping them into the dendrimer frame can improve many relevant biological properties, such as bioavailability, solubility, and selectivity. Directing groups to reach selective delivery in a specific organ is one of the advanced applications of PAMAM. In this review, structural and safety aspects of PAMAM and its derivatives are discussed, and some relevant applications are briefly presented. Emphasis has been given to gene delivery and targeting drugs, as advanced delivery systems using PAMAM and an incentive for its use on neglected diseases are briefly mentioned.

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“…This fluorescence enhancement allows direct in vivo bioimaging of the dendrimer nanoparticles without any need for conjugating traditional dyes or external staining. These studies demonstrated that pyrrolidone modified PAMAM-dendrimers manifest dramatically enhanced emission intensities (i.e., >50 fold) compared to unmodified amine terminated PAMAM dendrimers [ 28 , 29 ]. Recent proposed mechanisms to account for the NTIL phenomenon have concluded that these inexplicable blue emissions are largely due to the aggregation/clustering and/or physico-chemical confinement of normally non-emissive, electron-rich, hetero-atomic, functionalized moieties, (HASLs) (i.e., heteroatomic subluminophores) [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…As part of this quest, we turned our attention to tecto(dendrimers), a ternary conjugate of one large (core) dendrimer with a number of smaller ones at the periphery (shell) [ 36 , 37 , 48 ]. We decided to combine this approach with surface modification by pyrrolidone moieties, since they are known to confer biotolerance and enhance nontraditional intrinsic luminescence (NTIL) with the potential for direct bioimaging [ 24 , 26 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Internalization and Visualization of N-(4-Carbomethoxy) Pyrrolidone Terminated PAMAM [G5:G3-TREN] Tecto(dendrimers) in Mammalian Cells

et al. 2020

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Tecto(dendrimers) are well-defined, dendrimer cluster type covalent structures. In this article, we present the synthesis of such a PAMAM [G5:G3-(TREN)]-N-(4-carbomethoxy) pyrrolidone terminated tecto(dendrimer). This tecto(dendrimer) exhibits nontraditional intrinsic luminescence (NTIL; excitation 376 nm; emission 455 nm) that has been attributed to three fluorescent components characterized by different fluorescence lifetimes. Furthermore, it has been shown that this PAMAM [G5:G3-(TREN)]-N-(4-carbomethoxy) pyrrolidone terminated tecto(dendrimer) is able to form a polyplex with double stranded DNA, and is nontoxic for HeLa and HMEC-1 cells up to a concentration of 10 mg/mL, even though it accumulates in endosomal compartments as demonstrated by its unique NTIL emission properties. Many of the above features would portend the proposed use of this tecto(dendrimer) as an efficient transfection agent. Quite surprisingly, transfection activity could not be demonstrated in HeLa cells, and the possible reasons are discussed in the article.

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Modified PAMAM dendrimer with 4-carbomethoxypyrrolidone surface groups-its uptake, efflux, and location in a cell

Cited by 33 publications

References 13 publications

A Robust Intrinsically Green Fluorescent Poly(Amidoamine) Dendrimer for Imaging and Traceable Central Nervous System Delivery in Zebrafish

A Robust Intrinsically Green Fluorescent Poly(Amidoamine) Dendrimer for Imaging and Traceable Central Nervous System Delivery in Zebrafish

New Advances in General Biomedical Applications of PAMAM Dendrimers

Synthesis, Internalization and Visualization of N-(4-Carbomethoxy) Pyrrolidone Terminated PAMAM [G5:G3-TREN] Tecto(dendrimers) in Mammalian Cells

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